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Conserved domains on  [gi|10242292|gb|AAG15368|]
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GHRH receptor splice variant 1 [Homo sapiens]

Protein Classification

G protein-coupled receptor family protein( domain architecture ID 705710)

G protein-coupled receptor family protein is a seven-transmembrane G protein-coupled receptor (7TM-GPCR) family protein which typically transmits an extracellular signal into the cell by the conformational rearrangement of the 7TM helices and by the subsequent binding and activation of an intracellular heterotrimeric G protein; GPCR ligands include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tm_GPCRs super family cl28897
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
62-329 7.96e-167

seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.


The actual alignment was detected with superfamily member cd15270:

Pssm-ID: 475119 [Multi-domain]  Cd Length: 268  Bit Score: 466.20  E-value: 7.96e-167
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCSFSTVLCKVS 141
Cdd:cd15270   1 FSTVKIIYTVGYSISIVSLCVAVAILVAFRRLHCPRNYIHIQLFFTFILKAIAVFIKDAALFQEDDTDHCSMSTVLCKVS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 142 VAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSPYWWII 221
Cdd:cd15270  81 VVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKRYFWWLVLLGWGLPTLCTGTWILCKLYFEDTECWDINNDSPYWWII 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 222 KGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLGIRLPLELGLG 301
Cdd:cd15270 161 KGPIVISVGVNFLLFLNIIRILLKKLDPRQINFNNSAQYRRLSKSTLLLIPLFGTHYIIFNFLPDYAGLGIRLYLELCLG 240
                       250       260
                ....*....|....*....|....*...
gi 10242292 302 SFQGFIVAILYCFLNQEVRTEISRKWHG 329
Cdd:cd15270 241 SFQGFIVAVLYCFLNQEVQTEISRKWYG 268
 
Name Accession Description Interval E-value
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
62-329 7.96e-167

growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Growth hormone-releasing hormone receptor (GHRHR) is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, pituitary adenylate cyclase activating polypeptide (PACAP), and vasoactive intestinal peptide. These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. GHRH is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. GHRHR is found in mammals as well as zebrafish and chicken, whereas the GHRHR type 2, an ortholog of the GHRHR, has only been identified in ray-finned fish, chicken and Xenopus. Xenopus laevis GHRHR2 has been shown to interact with both endogenous GHRH and PACAP-related peptide (PRP).


Pssm-ID: 320398 [Multi-domain]  Cd Length: 268  Bit Score: 466.20  E-value: 7.96e-167
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCSFSTVLCKVS 141
Cdd:cd15270   1 FSTVKIIYTVGYSISIVSLCVAVAILVAFRRLHCPRNYIHIQLFFTFILKAIAVFIKDAALFQEDDTDHCSMSTVLCKVS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 142 VAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSPYWWII 221
Cdd:cd15270  81 VVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKRYFWWLVLLGWGLPTLCTGTWILCKLYFEDTECWDINNDSPYWWII 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 222 KGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLGIRLPLELGLG 301
Cdd:cd15270 161 KGPIVISVGVNFLLFLNIIRILLKKLDPRQINFNNSAQYRRLSKSTLLLIPLFGTHYIIFNFLPDYAGLGIRLYLELCLG 240
                       250       260
                ....*....|....*....|....*...
gi 10242292 302 SFQGFIVAILYCFLNQEVRTEISRKWHG 329
Cdd:cd15270 241 SFQGFIVAVLYCFLNQEVQTEISRKWYG 268
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
62-308 8.20e-95

7 transmembrane receptor (Secretin family); This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GCPRs). They have been described in many animal species, but not in plants, fungi or prokaryotes. Three distinct sub-families are recognized. Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways. Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin, and brain-specific angiogenesis inhibitors amongst others. Subfamily B3 includes Methuselah and other Drosophila proteins. Other than the typical seven-transmembrane region, characteriztic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling.


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 282.63  E-value: 8.20e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292    62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCsfSTVLCKVS 141
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKQDLDHC--SWVGCKVV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292   142 VAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSC--KLAFEDIACWDLDDTsPYWW 219
Cdd:pfam00002  79 AVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVdpKGYGEDDGCWLSNEN-GLWW 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292   220 IIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYI--IFNFLPDNAGLGIRLPLE 297
Cdd:pfam00002 158 IIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKQYRRLAKSTLLLLPLLGITWVfgLFAFNPENTLRVVFLYLF 237
                         250
                  ....*....|.
gi 10242292   298 LGLGSFQGFIV 308
Cdd:pfam00002 238 LILNSFQGFFV 248
 
Name Accession Description Interval E-value
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
62-329 7.96e-167

growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Growth hormone-releasing hormone receptor (GHRHR) is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, pituitary adenylate cyclase activating polypeptide (PACAP), and vasoactive intestinal peptide. These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. GHRH is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. GHRHR is found in mammals as well as zebrafish and chicken, whereas the GHRHR type 2, an ortholog of the GHRHR, has only been identified in ray-finned fish, chicken and Xenopus. Xenopus laevis GHRHR2 has been shown to interact with both endogenous GHRH and PACAP-related peptide (PRP).


Pssm-ID: 320398 [Multi-domain]  Cd Length: 268  Bit Score: 466.20  E-value: 7.96e-167
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCSFSTVLCKVS 141
Cdd:cd15270   1 FSTVKIIYTVGYSISIVSLCVAVAILVAFRRLHCPRNYIHIQLFFTFILKAIAVFIKDAALFQEDDTDHCSMSTVLCKVS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 142 VAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSPYWWII 221
Cdd:cd15270  81 VVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKRYFWWLVLLGWGLPTLCTGTWILCKLYFEDTECWDINNDSPYWWII 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 222 KGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLGIRLPLELGLG 301
Cdd:cd15270 161 KGPIVISVGVNFLLFLNIIRILLKKLDPRQINFNNSAQYRRLSKSTLLLIPLFGTHYIIFNFLPDYAGLGIRLYLELCLG 240
                       250       260
                ....*....|....*....|....*...
gi 10242292 302 SFQGFIVAILYCFLNQEVRTEISRKWHG 329
Cdd:cd15270 241 SFQGFIVAVLYCFLNQEVQTEISRKWYG 268
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
62-329 5.83e-130

secretin receptor-like group of hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group represents G protein-coupled receptors for structurally similar peptide hormones that include secretin, growth-hormone-releasing hormone (GHRH), pituitary adenylate cyclase activating polypeptide (PACAP), and vasoactive intestinal peptide (VIP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. Secretin, a polypeptide secreted by entero-endocrine S cells in the small intestine, is involved in maintaining body fluid balance. This polypeptide regulates the secretion of bile and bicarbonate into the duodenum from the pancreatic and biliary ducts, as well as regulates the duodenal pH by the control of gastric acid secretion. Studies with secretin receptor-null mice indicate that secretin plays a role in regulating renal water reabsorption. Secretin mediates its biological actions by elevating intracellular cAMP via G protein-coupled secretin receptors, which are expressed in the brain, pancreas, stomach, kidney, and liver. GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. All B1 subfamily GPCRs are able to increase intracellular cAMP levels by coupling to adenylate cyclase via a stimulatory Gs protein. However, depending on its cellular location, some members of subfamily B1 are also capable of coupling to additional G proteins such as G(i/o) and/or G(q) proteins, thereby leading to activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320596 [Multi-domain]  Cd Length: 268  Bit Score: 372.53  E-value: 5.83e-130
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCSFSTVLCKVS 141
Cdd:cd15930   1 YLTVKIIYTVGYSLSLTSLTTAMIILCLFRKLHCTRNYIHMNLFVSFILRAIAVFIKDAVLFSSEDVDHCFVSTVGCKAS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 142 VAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSPYWWII 221
Cdd:cd15930  81 MVFFQYCVMANFFWLLVEGLYLHTLLVISFFSERRYFWWYVLIGWGAPTVFVTVWIVARLYFEDTGCWDINDESPYWWII 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 222 KGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLGIRLPLELGLG 301
Cdd:cd15930 161 KGPILISILVNFVLFINIIRILLQKLRSPDIGGNESSQYKRLARSTLLLIPLFGIHYIVFAFFPENISLGIRLYFELCLG 240
                       250       260
                ....*....|....*....|....*...
gi 10242292 302 SFQGFIVAILYCFLNQEVRTEISRKWHG 329
Cdd:cd15930 241 SFQGFVVAVLYCFLNGEVQAEIKRKWRS 268
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
62-327 5.72e-111

growth-hormone-releasing hormone receptor type 2, member of the class B family of seven-transmembrane G protein-coupled receptors; Growth hormone-releasing hormone receptor type 2 (GHRHR2) is found in non-mammalian vertebrates such as chicken and frog. It is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal peptide, and mammalian growth hormone-releasing hormone. These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. Mammalian GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. Mammalian GHRH is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. GHRHR is found in mammals as well as zebrafish and chicken, whereas the GHRHR type 2, an ortholog of the GHRHR, has only been identified in ray-finned fish, chicken and Xenopus. Xenopus laevis GHRHR2 has been shown to interact with both endogenous GHRH and PACAP-related peptide (PRP).


Pssm-ID: 320399 [Multi-domain]  Cd Length: 267  Bit Score: 324.38  E-value: 5.72e-111
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCSFSTVLCKVS 141
Cdd:cd15271   1 FSTVKLLYTVGYGTSLTSLITAVLIFCTFRKLHCTRNYIHINLFVSFILRALAVFIKDAVLFADESVDHCTMSTVACKAA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 142 VAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDlDDTSPYWWII 221
Cdd:cd15271  81 VTFFQFCVLANFFWLLVEGMYLQTLLLLTFTSDRKYFWWYILIGWGAPSVTVTVWVLTRLQYDNRGCWD-DLESRIWWII 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 222 KGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLGIRLPLELGLG 301
Cdd:cd15271 160 KTPILLSVFVNFLIFINVIRILVQKLKSPDVGGNDTSHYMRLAKSTLLLIPLFGVHYVVFAFFPEHVGVEARLYFELVLG 239
                       250       260
                ....*....|....*....|....*.
gi 10242292 302 SFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15271 240 SFQGFIVALLYCFLNGEVQAEIKKRL 265
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
62-327 4.15e-105

secretin receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Secretin receptor is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include vasoactive intestinal peptide (VIP), growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors, and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. Secretin, a polypeptide secreted by entero-endocrine S cells in the small intestine, is involved in maintaining body fluid balance. This polypeptide regulates the secretion of bile and bicarbonate into the duodenum from the pancreatic and biliary ducts, as well as regulates the duodenal pH by the control of gastric acid secretion. Studies with secretin receptor-null mice indicate that secretin plays a role in regulating renal water reabsorption. Secretin mediates its biological actions by elevating intracellular cAMP via G protein-coupled secretin receptor, which is expressed in the brain, pancreas, stomach, kidney, and liver.


Pssm-ID: 320403 [Multi-domain]  Cd Length: 271  Bit Score: 309.75  E-value: 4.15e-105
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCSFSTVLCKVS 141
Cdd:cd15275   1 FMYLKTMYTVGYSVSLVSLAIALAILCSFRRLHCTRNYIHMQLFLSFILRAISIFIKDAVLFSSEDDNHCDIYTVGCKVA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 142 VAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSPYWWII 221
Cdd:cd15275  81 MVFSNYCIMANYSWLLVEGLYLHSLLSISFFSERKHLWWYIALGWGSPLIFIISWAIARYLHENEGCWDTRRNAWIWWII 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 222 KGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLG---IRLPLEL 298
Cdd:cd15275 161 RGPVILSIFVNFILFLNILRILMRKLRAPDMRGNEFSQYKRLAKSTLLLIPLFGLHYILFAFFPEDVSSGtmeIWLFFEL 240
                       250       260
                ....*....|....*....|....*....
gi 10242292 299 GLGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15275 241 ALGSFQGFVVAVLYCFLNGEVQLEIQRKW 269
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
62-327 3.00e-101

vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of seven-transmembrane G protein-coupled receptors; Vasoactive intestinal peptide (VIP) receptor 1 is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. VIP-R1 is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. However, depending on its cellular location, VIP-R1 is also capable of coupling to additional G proteins such as G(q) protein, thus leading to the activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320397 [Multi-domain]  Cd Length: 268  Bit Score: 299.85  E-value: 3.00e-101
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCSFSTVLCKVS 141
Cdd:cd15269   1 FGTVKTGYTIGHSLSLISLTAAMIILCLFRKLHCTRNYIHMHLFMSFILRAIAVFIKDAVLFESGEEDHCSVASVGCKAA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 142 VAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSPYWWII 221
Cdd:cd15269  81 MVFFQYCIMANFFWLLVEGLYLHTLLAVSFFSERKYFWWYILIGWGAPSVFITAWSVARIYFEDVGCWDTIIESLLWWII 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 222 KGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLGIRLPLELGLG 301
Cdd:cd15269 161 KTPILVSILVNFILFICIIRILVQKLHSPDIGRNESSQYSRLAKSTLLLIPLFGIHYIMFAFFPDNFKAEVKLVFELILG 240
                       250       260
                ....*....|....*....|....*.
gi 10242292 302 SFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15269 241 SFQGFVVAVLYCFLNGEVQAELKRKW 266
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
62-308 8.20e-95

7 transmembrane receptor (Secretin family); This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GCPRs). They have been described in many animal species, but not in plants, fungi or prokaryotes. Three distinct sub-families are recognized. Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways. Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin, and brain-specific angiogenesis inhibitors amongst others. Subfamily B3 includes Methuselah and other Drosophila proteins. Other than the typical seven-transmembrane region, characteriztic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling.


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 282.63  E-value: 8.20e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292    62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCsfSTVLCKVS 141
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKQDLDHC--SWVGCKVV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292   142 VAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSC--KLAFEDIACWDLDDTsPYWW 219
Cdd:pfam00002  79 AVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVdpKGYGEDDGCWLSNEN-GLWW 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292   220 IIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYI--IFNFLPDNAGLGIRLPLE 297
Cdd:pfam00002 158 IIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKQYRRLAKSTLLLLPLLGITWVfgLFAFNPENTLRVVFLYLF 237
                         250
                  ....*....|.
gi 10242292   298 LGLGSFQGFIV 308
Cdd:pfam00002 238 LILNSFQGFFV 248
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
62-327 5.98e-91

parathyroid hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone (PTH) receptor family has three subtypes: PTH1R, PTH2R and PTH3R. PTH1R is expressed in bone and kidney and is activated by two polypeptide ligands: PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH1R couples predominantly to a G(s)-protein that in turn activates adenylate cyclase thereby producing cAMP, but it can also couple to several G protein subtypes, including G(q/11), G(i/o), and G(12/13), resulting in activation of multiple intracellular signaling pathways. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39), but not by PTHrP. PTH also strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs, suggesting that TIP-39 is a natural ligand for PTH2R. On the other hand, PTH3R binds and responds to both PTH and PTHrP, but not the TIP-39. Moreover, the PTH3R is more closely related to the PTH1R than PTH2R. PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. The PTH3R is found in chicken and fish, but it is absent in mammals. The PTH receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways.


Pssm-ID: 320393 [Multi-domain]  Cd Length: 289  Bit Score: 274.25  E-value: 5.98e-91
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALfHSDDT------------- 128
Cdd:cd15265   1 FERLYLIYTVGYSISLVSLTVAVFILGYFRRLHCTRNYIHMHLFVSFMLRAVSIFVKDAVL-YSGSGldelerpsmedlk 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 129 ------DHCSFSTVLCKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLA 202
Cdd:cd15265  80 siveapPVDKSQYVGCKVAVTLFLYFLATNYYWILVEGLYLHSLIFMAFFSDKKYLWGFTLIGWGFPAVFVIPWASVRAT 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 203 FEDIACWDLDDTSpYWWIIKGPIVLSVGVNFGLFLNIIRILVRKL-EPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIF 281
Cdd:cd15265 160 LADTRCWDLSAGN-YKWIYQVPILAAIVVNFILFLNIVRVLATKLrETNAGRCDTRQQYRKLAKSTLVLIPLFGVHYIVF 238
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 10242292 282 NFLPDN-AGLG--IRLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15265 239 MGMPYTeVGLLwqIRMHYELFFNSFQGFFVAIIYCFCNGEVQAEIKKRW 287
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
62-329 2.72e-90

pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PACAP-R1) is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), and vasoactive intestinal peptide (VIP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. PACAP-R1 is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level.


Pssm-ID: 320653 [Multi-domain]  Cd Length: 268  Bit Score: 271.84  E-value: 2.72e-90
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCSFSTVLCKVS 141
Cdd:cd15987   1 YLSVKALYTVGYSTSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIKDGVLYAEQDSDHCFVSTVECKAV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 142 VAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSPYWWII 221
Cdd:cd15987  81 MVFFHYCVMSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTICVTVWAVLRLHFDDTGCWDMNDNTALWWVI 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 222 KGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLGIRLPLELGLG 301
Cdd:cd15987 161 KGPVVGSIMINFVLFIGIIIILVQKLQSPDIGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGLG 240
                       250       260
                ....*....|....*....|....*...
gi 10242292 302 SFQGFIVAILYCFLNQEVRTEISRKWHG 329
Cdd:cd15987 241 SFQGFVVAVLYCFLNGEVQSEIKRKWRS 268
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
62-327 1.23e-85

vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of seven-transmembrane G protein-coupled receptors; Vasoactive intestinal peptide (VIP) receptor 2 is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. VIP-R1 is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. However, depending on its cellular location, VIP-R1 is also capable of coupling to additional G proteins such as G(q) protein, thus leading to the activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320652 [Multi-domain]  Cd Length: 269  Bit Score: 260.12  E-value: 1.23e-85
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCSFSTVL--CK 139
Cdd:cd15986   1 YIVVKTIYTLGHSVSLIALTTGSTILCLFRKLHCTRNYIHLNLFFSFILRAISVLVKDDILYSSSNTEHCTVPPSLigCK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 140 VSVAASHFATMTNFSWLLAEAVYLNCLLASTSpSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSPYWW 219
Cdd:cd15986  81 VSLVILQYCIMANFYWLLVEGLYLHTLLVVIF-SENRHFIVYLLIGWGIPTVFIIAWIVARIYLEDTGCWDTNDHSVPWW 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 220 IIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLGIRLPLELG 299
Cdd:cd15986 160 VIRIPIIISIILNFILFISIIRILLQKLRSPDVGGNDQSQYKRLAKSTLLLIPLFGVHYIVFVYFPDSSSSNYQIFFELC 239
                       250       260
                ....*....|....*....|....*...
gi 10242292 300 LGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15986 240 LGSFQGLVVAILYCFLNSEVQGELKRKW 267
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
62-329 9.82e-84

glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G protein-coupled receptors; This group represents the glucagon receptor family of G protein-coupled receptors, which includes glucagon receptor (GCGR), glucagon-like peptide-1 receptor (GLP1R), GLP2R, and closely related receptors. These receptors are activated by the members of the glucagon (GCG) peptide family including GCG, glucagon-like peptide 1 (GLP1), and GLP2, which are derived from the large proglucagon precursor. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. Receptors in this group belong to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 341353 [Multi-domain]  Cd Length: 279  Bit Score: 255.44  E-value: 9.82e-84
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALF--HSDDTDHCSFSTVL-- 137
Cdd:cd15929   1 LSSLQVMYTVGYSLSLAALVLALAILLGLRKLHCTRNYIHANLFASFILRALSVLVKDALLPrrYSQKGDQDLWSTLLsn 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 138 -----CKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLD 212
Cdd:cd15929  81 qaslgCRVAQVLMQYCVAANYYWLLVEGLYLHTLLVLAVFSERSIFRLYLLLGWGAPVLFVVPWGIVKYLYENTGCWTRN 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 213 DTSPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQgsLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLG- 291
Cdd:cd15929 161 DNMAYWWIIRLPILLAILINFFIFVRILKILVSKLRANQ--MCKTDYKFRLAKSTLTLIPLLGVHEVVFAFVTDEQARGt 238
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 10242292 292 ---IRLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKWHG 329
Cdd:cd15929 239 lrfIKLFFELFLSSFQGLLVAVLYCFANKEVQSELRKKWHR 279
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
62-328 3.81e-81

The subfamily B1 of hormone receptors (secretin-like), member of the class B family seven-transmembrane G protein-coupled receptors; The B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of this subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. Moreover, the B1 subfamily receptors play key roles in hormone homeostasis and are promising drug targets in various human diseases including diabetes, osteoporosis, obesity, neurodegenerative conditions (Alzheimer###s and Parkinson's), cardiovascular disease, migraine, and psychiatric disorders (anxiety, depression). Furthermore, the subfamilies B2 and B3 consist of receptors that are capable of interacting with epidermal growth factors (EGF) and the Drosophila melanogaster Methuselah gene product (Mth), respectively. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 341321 [Multi-domain]  Cd Length: 273  Bit Score: 248.68  E-value: 3.81e-81
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAaLFHSDDTDHCSFSTVL---- 137
Cdd:cd15041   1 LLVVYYIYLVGYSLSLVALLPAIVIFLYFRSLRCTRIRLHINLFLSFILRAVFWIIWDL-LVVYDRLTSSGVETVLmqnp 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 138 --CKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTS 215
Cdd:cd15041  80 vgCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAFFSEPSSLKLYYAIGWGLPLVIVVIWAIVRALLSNESCWISYNNG 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 216 PYWWIIKGPIVLSVGVNFGLFLNIIRILVRKLepaQGSLHTQ-SQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLG--I 292
Cdd:cd15041 160 HYEWILYGPNLLALLVNLFFLINILRILLTKL---RSHPNAEpSNYRKAVKATLILIPLFGIQYLLTIYRPPDGSEGelV 236
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 10242292 293 RLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKWH 328
Cdd:cd15041 237 YEYFNAILNSSQGFFVAVIYCFLNGEVQSELKRKWS 272
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
63-327 3.90e-76

glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Glucagon-like peptide-2 receptor (GLP2R) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon receptor (GCGR) and GLP1R. GLP2R is activated by glucagon-like peptide 2, which is derived from the large proglucagon precursor. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. GLP2R belongs to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320394 [Multi-domain]  Cd Length: 280  Bit Score: 236.18  E-value: 3.90e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  63 STVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHS------DDTDHCSF--- 133
Cdd:cd15266   2 LTLQLIYTIGYSLSLISLSLALLILLLLRKLHCTRNYIHMNLFASFILRALAVLIKDIVLYSTyskrpdDETGWISYlse 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 134 -STVLCKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLD 212
Cdd:cd15266  82 eSSTSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSERRLLKKYMLIGWGTPVLFVVPWGVAKILLENTGCWGRN 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 213 DTSPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSqyWRLSKSTLFLIPLFGIHYIIFNFLPDN----A 288
Cdd:cd15266 162 ENMGIWWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQMRFTDYK--YRLARSTLVLIPLLGIHEVVFSFITDEqvegF 239
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 10242292 289 GLGIRLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15266 240 SRHIRLFIQLTLSSFQGFLVAVLYCFANGEVKAELKKRW 278
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
65-328 1.93e-75

invertebrate parathyroid hormone-related receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes parathyroid hormone (PTH)-related receptors found in invertebrates such as mollusks and annelid worms. The PTH family receptors are members of the B1 subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. The parathyroid hormone type 1 receptor (PTH1R) is found in all vertebrate species and is activated by two polypeptide ligands: parathyroid hormone (PTH), an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH1R couples predominantly to G(s)- protein that in turn activates adenylyl cyclase thereby producing cAMP, but it can also couple to several G protein subtypes, including G(q/11), G(i/o), and G(12/13), resulting in activation of multiple signaling pathways.


Pssm-ID: 320400 [Multi-domain]  Cd Length: 285  Bit Score: 234.59  E-value: 1.93e-75
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  65 VKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAAL-----FHSDDTDHCSFSTVL-- 137
Cdd:cd15272   4 IRLMYNIGYGLSLVSLLIAVIIMLYFKKLHCPRNTIHINLFVSFILRAVLSFIKENLLvqgvgFPGDVYYDSNGVIEFkd 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 138 ------CKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDL 211
Cdd:cd15272  84 egshweCKLFFTMFNYILGANYMWIFVEGLYLHMLIFVAVFSENSRVKWYILLGWLSPLLFVLPWVFVRATLEDTLCWNT 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 212 DDTSPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLG 291
Cdd:cd15272 164 NTNKGYFWIIRGPIVISIAINFLFFINIVRVLFTKLKASNTQESRPFRYRKLAKSTLVLIPLFGVHYMVFVVLPDSMSSD 243
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 10242292 292 ----IRLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKWH 328
Cdd:cd15272 244 eaelVWLYFEMFFNSFQGFIVALLFCFLNGEVQSEIKKKWQ 284
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
62-327 2.72e-70

parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone (PTH) receptor family has three subtypes: PTH1R, PTH2R and PTH3R. PTH1R is expressed in bone and kidney and is activated by two polypeptide ligands: PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH1R couples predominantly to G(s)-protein that in turn activates adenylate cyclase thereby producing cAMP, but it can also couple to several G protein subtypes, including G(q/11), G(i/o), and G(12/13), resulting in activation of multiple intracellular signaling pathways. PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. PTH3R is found in chicken and fish, but it is absent in mammals. The PTH receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways.


Pssm-ID: 320650 [Multi-domain]  Cd Length: 290  Bit Score: 221.36  E-value: 2.72e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCSFST------ 135
Cdd:cd15984   1 FDRLYLIYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGSALEEMERITeedlks 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 136 ------------VLCKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAF 203
Cdd:cd15984  81 iteappadkaqfVGCKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVFVTIWASVRATL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 204 EDIACWDLdDTSPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKL-EPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFN 282
Cdd:cd15984 161 ADTGCWDL-SAGNLKWIIQVPILAAIVVNFILFINIVRVLATKLrETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIVFM 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 10242292 283 FLPDNAGLGI----RLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15984 240 AMPYTEVSGIlwqvQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSW 288
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
61-328 1.25e-69

glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Glucagon receptor (GCGR) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon-like peptide-1 receptor (GLP1R) and GLP2R. GCGR is activated by glucagon, which is derived from the large proglucagon precursor. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. GCGR belongs to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320395 [Multi-domain]  Cd Length: 281  Bit Score: 219.31  E-value: 1.25e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  61 YFSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHS-----DDTDHCSF-- 133
Cdd:cd15267   2 TYSSFQVMYTVGYSLSLGALLLALAILGGFSKLHCMRNAIHMNLFASFILKASSVLVIDGLLRTRysqkiEDDLSSTWls 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 134 --STVLCKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDL 211
Cdd:cd15267  82 deAVAGCRVAAVFMQYGIVANYCWLLVEGIYLHNLLVLAVFPERSYFSLYLCIGWGAPALFVVPWVVVKCLYENVQCWTS 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 212 DDTSPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQgsLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLG 291
Cdd:cd15267 162 NDNMGFWWILRFPVFLAILINFFIFVRIIQILVSKLRARQ--MHYTDYKFRLAKSTLTLIPLLGIHEVVFAFVTDEHAQG 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|.
gi 10242292 292 ----IRLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKWH 328
Cdd:cd15267 240 tlrsAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWH 280
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
65-327 2.13e-68

insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of seven-transmembrane G protein-coupled receptors; This subgroup includes a neuropeptide receptor found in Nilaparvata lugens (brown planthopper) and its closely related proteins from invertebrates. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 320401 [Multi-domain]  Cd Length: 285  Bit Score: 216.47  E-value: 2.13e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  65 VKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKD-------AALFHSDDTDHCSF---- 133
Cdd:cd15273   4 IKGISQIGYIVSLITLIIAFAIFLSFKKLHCARNKLHMHLFASFILRAFMTLLKDslfidglGLLADIVERNGGGNevia 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 134 ---STVLCKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWD 210
Cdd:cd15273  84 nigSNWVCKAITSLWQYFIIANYSWILMEGLYLHNLIFLALFSDENNIILYILLGWGLPLIFVVPWIVARILFENSLCWT 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 211 LDDTSPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKLepaQGSLHTQSQ-YWRLSKSTLFLIPLFGIHYIIFNFLPDNAG 289
Cdd:cd15273 164 TNSNLLNFLIIRIPIMISVLINFILFLNIVRVLLVKL---RSSVNEDSRrYKKWAKSTLVLVPLFGVHYTIFLILSYLDD 240
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 10242292 290 LGIRLPL-----ELGLGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15273 241 TNEAVELiwlfcDQLFASFQGFFVALLYCFLNGEVRAEIQRKW 283
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
62-327 1.41e-67

parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone 3 receptor (PTH3R), one of the three subtypes of PTH receptor family, is found in chicken and fish, but it is absent in mammals. On the other hand, the PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. PTH1R is activated by two polypeptide ligands: PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39), but not by PTHrP. PTH also strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs, suggesting that TIP-39 is a natural ligand for PTH2R. Conversely, PTH3R binds and responds to both PTH and PTHrP, but not the TIP-39. The PTH family receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways.


Pssm-ID: 320649 [Multi-domain]  Cd Length: 285  Bit Score: 214.40  E-value: 1.41e-67
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTDHCSFSTVL---- 137
Cdd:cd15983   1 FERLHLMYTIGYSISLAALLVAVCILCYFKRLHCTRNYIHIHLFASFICRAGSIFVKDAVLYSGTNEGEALDEKIEfgls 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 138 ---------CKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIAC 208
Cdd:cd15983  81 pgtrlqwvgCKVTVTLFLYFLATNHYWILVEGLYLHSLIFMAFLSDKNYLWALTIIGWGLPAVFVSVWASVRVSLADTQC 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 209 WDLdDTSPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKL-EPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLP-- 285
Cdd:cd15983 161 WDL-SAGNLKWIYQVPILAAILVNFFLFLNIVRVLASKLwETNTGKLDPRQQYRKLLKSTLVLMPLFGVHYVLFMAMPyt 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....
gi 10242292 286 DNAGL--GIRLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15983 240 DVTGLlwQIQMHYEMLFNSSQGFFVAFIYCFCNGEVQAEIKKAW 283
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
62-327 1.01e-63

parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone 2 receptor (PTH2R), one of the three subtypes of PTH receptor family, is found in mammals and fish, but not in chicken or frog. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39) but not by PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs. These results suggest that TIP-39 is a natural ligand for PTH2R. Conversely, PTH1R is activated by PTH and PTHrP, but not by TIP-39. The PTH family receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways.


Pssm-ID: 320648 [Multi-domain]  Cd Length: 289  Bit Score: 204.40  E-value: 1.01e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDA------------ALFHSDDTD 129
Cdd:cd15982   1 FERLYIMYTVGYSISFSSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAASIFVKDKvvhthigvkeldAVLMNDFQN 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 130 HCSFSTVL------CKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAF 203
Cdd:cd15982  81 AVDAPPVDksqyvgCKIAVVMFIYFLATNYYWILVEGLYLHSLIFVAFFSDTKYLWGFTLIGWGFPAVFVAAWAVVRATL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 204 EDIACWDLdDTSPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKL-EPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFN 282
Cdd:cd15982 161 ADARCWEL-SAGDIKWIYQAPILAAIGLNFILFLNTVRVLATKIwETNAVGYDTRKQYRKLAKSTLVLVLVFGVHYIVFV 239
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*...
gi 10242292 283 FLPDN-AGLG--IRLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15982 240 CLPHTfTGLGweIRMHCELFFNSFQGFFVSIIYCYCNGEVQTEIKKTW 287
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
67-327 1.69e-61

glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Glucagon-like peptide-1 receptor (GLP1R) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon receptor and GLP2R. GLP1R is activated by glucagon-like peptide 1 (GLP1), which is derived from the large proglucagon precursor. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. Receptors in this group belong to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 341342 [Multi-domain]  Cd Length: 279  Bit Score: 198.64  E-value: 1.69e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAAL--FHSDDTDHCSFSTVL------- 137
Cdd:cd15268   6 IIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALkwMYSTAAQQHQWDGLLsyqdsls 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 138 CKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSPY 217
Cdd:cd15268  86 CRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVFSEQRIFRLYLSIGWGVPLLFVIPWGIVKYLYEDEGCWTRNSNMNY 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 218 WWIIKGPIVLSVGVNFGLFLNIIRILVRKLepaQGSLHTQSQY-WRLSKSTLFLIPLFGIHYIIFNFLPDNAGLG----I 292
Cdd:cd15268 166 WLIIRLPILFAIGVNFLIFIRVICIVVSKL---KANLMCKTDIkCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGtlrfV 242
                       250       260       270
                ....*....|....*....|....*....|....*
gi 10242292 293 RLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15268 243 KLFTELSFTSFQGLMVAILYCFVNNEVQMEFRKSW 277
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
64-327 1.70e-60

uncharacterized group of glucagon receptor-like proteins, member of the class B family of seven-transmembrane G protein-coupled receptors; This group consists of uncharacterized proteins with similarity to members of the glucagon receptor family of G protein-coupled receptors, which include glucagon receptor (GCGR), and glucagon-like peptide-1 receptor (GLP1R), and GLP2R. The glucagon receptors are activated by the members of the glucagon (GCG) peptide family including GCG, glucagon-like peptide 1 (GLP1), and GLP2, which are derived from the large proglucagon precursor. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. Receptors in this group belong to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320651 [Multi-domain]  Cd Length: 280  Bit Score: 195.92  E-value: 1.70e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  64 TVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFH---------SDDTDHCSFS 134
Cdd:cd15985   3 SFRMLYTVGYTLSLLTLVSALLILTSIRKLHCTRNYIHANLFASFILRAVSVIVKDTLLERrwgreimrvADWGELLSHK 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 135 TVL-CKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDD 213
Cdd:cd15985  83 AAIgCRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYLYLGWGTPVLFVVPWMLAKYLKENKECWALNE 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 214 TSPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLhtQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLG-- 291
Cdd:cd15985 163 NMAYWWIIRIPILLASLINLLIFMRILKVILSKLRANQKGY--ADYKLRLAKATLTLIPLFGIHEVVFIFATDEQTTGil 240
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 10242292 292 --IRLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15985 241 ryIKVFFTLFLNSFQGFLVAVLYCFANKEVKSELLKKW 278
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
62-328 3.37e-55

corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320392 [Multi-domain]  Cd Length: 265  Bit Score: 181.85  E-value: 3.37e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  62 FSTVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLkdaaLFHSDDTDHCSFSTVLCKVS 141
Cdd:cd15264   1 YKVALIIYYLGFSISLVALAVALIIFLYFRSLRCLRNNIHCNLIVTFILRNVTWFI----MQNTLTEIHHQSNQWVCRLI 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 142 VAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACW-DLDDTSPYWWI 220
Cdd:cd15264  77 VTVYNYFQVTNFFWMFVEGLYLHTMIVWAYSADKIRFWYYIVIGWCIPCPFVLAWAIVKLLYENEHCWlPKSENSYYDYI 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 221 IKGPIVLSVGVNFGLFLNIIRILVRKLEpAQGSLHTQsQYWRLSKSTLFLIPLFGIHYIIFnFLPDNAGLGIRLPLELG- 299
Cdd:cd15264 157 YQGPILLVLLINFIFLFNIVWVLITKLR-ASNTLETI-QYRKAVKATLVLLPLLGITYMLF-FINPGDDKTSRLVFIYFn 233
                       250       260       270
                ....*....|....*....|....*....|.
gi 10242292 300 --LGSFQGFIVAILYCFLNQEVRTEISRKWH 328
Cdd:cd15264 234 tfLQSFQGLFVAVFYCFLNGEVRSAIRKKFS 264
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
68-328 6.28e-50

insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of seven-transmembrane G protein-coupled receptors; This subgroup includes a neuropeptide receptor found in Nilaparvata lugens (brown planthopper) and its closely related proteins from mollusks and annelid worms. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 320388 [Multi-domain]  Cd Length: 267  Bit Score: 168.22  E-value: 6.28e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  68 IYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILkAGAVFLKDAALFHsDDTDHCSFSTVLCKVSVAASHF 147
Cdd:cd15260   7 VYIGGYSVSLIALIISLAIFFSFRSLRCTRITIHMNLFISFAL-NNLLWIVWYKLVV-DNPEVLLENPIWCQALHVLLQY 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 148 ATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFED--IACWdLDDtSPYWWIIKGPI 225
Cdd:cd15260  85 FMVCNYFWMFCEGLYLHTVLVVAFISEKSLMRWFIAIGWGVPLVITAIYAGVRASLPDdtERCW-MEE-SSYQWILIVPV 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 226 VLSVGVNFGLFLNIIRILVRKLePAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGlgirlPLELG------ 299
Cdd:cd15260 163 VLSLLINLIFLINIVRVLLTKL-RATSPNPAPAGLRKAVRATLILIPLLGLQFLLIPFRPEPGA-----PLETIyqyvsa 236
                       250       260       270
                ....*....|....*....|....*....|
gi 10242292 300 -LGSFQGFIVAILYCFLNQEVRTEISRKWH 328
Cdd:cd15260 237 lLTSLQGLCVAVLFCFCNGEVIAAIKRKWR 266
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
67-328 4.45e-43

corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320561 [Multi-domain]  Cd Length: 265  Bit Score: 150.09  E-value: 4.45e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDdtdHCSfSTVLCKVSVAASH 146
Cdd:cd15445   6 IINYLGHCISLVALLVAFVLFLRLRSIRCLRNIIHWNLITAFILRNATWFVVQLTMSPEV---HQS-NVVWCRLVTAAYN 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 147 FATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSPYW-WIIKGPI 225
Cdd:cd15445  82 YFHVTNFFWMFGEGCYLHTAIVLTYSTDKLRKWMFICIGWCIPFPIIVAWAIGKLYYDNEKCWFGKRAGVYTdYIYQGPM 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 226 VLSVGVNFGLFLNIIRILVRKLEPAQGSlhTQSQYWRLSKSTLFLIPLFGIHYIIFNFLP--DNAGLGIRLPLELGLGSF 303
Cdd:cd15445 162 ILVLLINFIFLFNIVRILMTKLRASTTS--ETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDEISRIVFIYFNSFLESF 239
                       250       260
                ....*....|....*....|....*
gi 10242292 304 QGFIVAILYCFLNQEVRTEISRKWH 328
Cdd:cd15445 240 QGFFVSVFYCFLNSEVRSAVRKRWH 264
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
63-323 2.98e-42

class B family of seven-transmembrane G protein-coupled receptors; The class B of seven-transmembrane GPCRs is classified into three major subfamilies: subfamily B1 (secretin-like receptor family), B2 (adhesion family), and B3 (Methuselah-like family). The class B receptors have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi or prokaryotes. The B1 subfamily comprises receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the subfamily B1 receptors preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The subfamily B2 consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. Furthermore, the subfamily B3 includes Methuselah (Mth) protein, which was originally identified in Drosophila as a GPCR affecting stress resistance and aging, and its closely related proteins.


Pssm-ID: 410627 [Multi-domain]  Cd Length: 260  Bit Score: 147.74  E-value: 2.98e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  63 STVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILkAGAVFLKDAALFHSDDtdhcsfsTVLCKVSV 142
Cdd:cd13952   2 LALSIITYIGCSLSLVGLLLTIITYLLFPKLRNLRGKILINLCLSLLL-AQLLFLIGQLLTSSDR-------PVLCKALA 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 143 AASHFATMTNFSWLLAEAVYLNCLLASTSP-SSRRAFWWLVLAGWGLPVLFTGTWV-------SCKLAFEDIACWdLDDT 214
Cdd:cd13952  74 ILLHYFLLASFFWMLVEAFDLYRTFVKVFGsSERRRFLKYSLYGWGLPLLIVIITAivdfslyGPSPGYGGEYCW-LSNG 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 215 SPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKLEpAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLGIRL 294
Cdd:cd13952 153 NALLWAFYGPVLLILLVNLVFFILTVRILLRKLR-ETPKQSERKSDRKQLRAYLKLFPLMGLTWIFGILAPFVGGSLVFW 231
                       250       260
                ....*....|....*....|....*....
gi 10242292 295 PLELGLGSFQGFIVAILYCFLNQEVRTEI 323
Cdd:cd13952 232 YLFDILNSLQGFFIFLIFCLKNKEVRRLL 260
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
67-328 9.36e-41

corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320562 [Multi-domain]  Cd Length: 264  Bit Score: 144.33  E-value: 9.36e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLkdaaLFHSDDTDHCSfSTVLCKVSVAASH 146
Cdd:cd15446   6 IINYLGHCISVGALVVAFLLFLCLRSIRCLRNIIHWNLITTFILRNVMWFL----LQMIDHNIHES-NEVWCRCITTIYN 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 147 FATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSPYW-WIIKGPI 225
Cdd:cd15446  81 YFVVTNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFLFIGWCIPCPIIVAWAIGKLYYENEQCWFGKEPGKYIdYIYQGPV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 226 VLSVGVNFGLFLNIIRILVRKLEPAQGSlhTQSQYWRLSKSTLFLIPLFGIHYIIFNFLP--DNAGLGIRLPLELGLGSF 303
Cdd:cd15446 161 ILVLLINFVFLFNIVRILMTKLRASTTS--ETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDDISQIVFIYFNSFLQSF 238
                       250       260
                ....*....|....*....|....*
gi 10242292 304 QGFIVAILYCFLNQEVRTEISRKWH 328
Cdd:cd15446 239 QGFFVSVFYCFLNGEVRSAARKRWH 263
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
71-327 9.46e-39

calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes G protein-coupled receptors for calcitonin (CT) and calcitonin gene-related peptides (CGRPs). Calcitonin, a 32-amino acid peptide hormone, is involved in calcium metabolism in many mammalian species and acts to reduce blood calcium levels and directly inhibits bone resorption by acting on osteoclast. Thus, CT acts as an antagonist to parathyroid hormone and is commonly used in the treatment of bone disorders. The CT receptor is predominantly found in osteoclasts, kidney, and brain, and is primarily coupled to stimulatory G(s) protein, which leads to activation of adenylate cyclase, thereby increasing cAMP production. CGRP, a member of the calcitonin family of peptides, is a potent vasodilator and may contribute to migraine. It is expressed in the peripheral and central nervous system and exists in two forms in humans (alpha-CGRP and beta-CGRP). CGRP meditates its physiological effects through calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1), a single transmembrane domain protein. Thus, the CRLR/RAMP1 complex serves as a functional CGRP receptor. On the other hand, the CRLR/RAMP2 and CRLR/RAMP3 complexes function as adrenomedullin-specific receptors. The CT and CGRP receptors belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide.


Pssm-ID: 341343 [Multi-domain]  Cd Length: 274  Bit Score: 139.14  E-value: 9.46e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  71 VGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAAlfHSDDTDHCSFSTVLCKVSVAASHFATM 150
Cdd:cd15274  10 VGHSLSIATLLISLGIFFFFRSLSCQRVTLHKNLFLSYILNSIIIIIHLVA--VVPNGELVARNPVSCKILHFIHQYMMG 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 151 TNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIACWDLDDTSpYWWIIKGPIVLSVG 230
Cdd:cd15274  88 CNYFWMLCEGIYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHAITRAVYYNDNCWLSSETH-LLYIIHGPIMAALV 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 231 VNFGLFLNIIRILVRKLEPAQGSlhTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLG-IRLPLELGLGSFQGFIVA 309
Cdd:cd15274 167 VNFFFLLNIVRVLVTKLRETHEA--ESHMYLKAVKATLILVPLLGIQFVLFPWRPSGKILGkIYDYVMHSLIHFQGFFVA 244
                       250
                ....*....|....*...
gi 10242292 310 ILYCFLNQEVRTEISRKW 327
Cdd:cd15274 245 TIFCFCNGEVQATLKRQW 262
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
65-327 1.21e-35

The pigment dispersing factor receptor, member of the class B seven-transmembrane G protein-coupled receptors; The pigment dispersing factor receptor (PDFR) is a G protein-coupled receptor that binds the circadian clock neuropeptide PDF, a functional ortholog of the mammalian vasoactive intestinal peptide (VIP), on the pacemaker neurons. The PDFR is implicated in regulating flight circuit development and in modulating acute flight In Drosophila melanogaster. The PDFR activation stimulates adenylate cyclase, thereby increasing cAMP levels in many different pacemakers, and the receptor signaling has been shown to regulate behavioral circadian rhythms and geotaxis in Drosophila. The PDFR belongs to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. . These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. They play key roles in hormone homeostasis in mammals and are promising drug targets in various human diseases including diabetes, osteoporosis, obesity, neurodegenerative conditions (Alzheimer###s and Parkinson's), cardiovascular disease, migraine, and psychiatric disorders (anxiety, depression).


Pssm-ID: 320389 [Multi-domain]  Cd Length: 282  Bit Score: 130.95  E-value: 1.21e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  65 VKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKA--GAVFLKDAALFHSDDTDHCSFST------- 135
Cdd:cd15261   4 TRTLEIVGLCLSLVSLIISLFIFSYFRTLRNHRTRIHKNLFLAILLQViiRLVLYIDQAITRSRGSHTNAATTegrtins 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 136 --VLCKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDI-ACWDLD 212
Cdd:cd15261  84 tpILCEGFYVLLEYAKTVMFMWMFIEGLYLHNIIVVSVFSGKPNYLFYYILGWGIPIVHTSAWAIVTLIKMKVnRCWFGY 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 213 DTSPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQywRLSKSTLFLIPLFGI----HYIIFNFLPDNA 288
Cdd:cd15261 164 YLTPYYWILEGPRLAVILINLFFLLNIIRVLVSKLRESHSREIEQVR--KAVKAAIVLLPLLGItnilQMIPPPLTSVIV 241
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 10242292 289 GLGIRLPLELGLGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15261 242 GFAVWSYSTHFLTSFQGFFVALIYCFLNGEVKNVLKKFW 280
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
67-327 2.23e-35

insect diuretic hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes G protein-coupled receptors that specifically bind to insect diuretic hormones found in Manduca sexta (moth) and Acheta domesticus (the house cricket), among others. Insect diuretic hormone and their GPCRs play critical roles in the regulation of water and ion balance. Thus they are attractive targets for developing new insecticides. Activation of the diuretic hormone receptors stimulate adenylate cyclase, thereby increasing cAMP levels in Malpighian tube. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of Gs family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx.


Pssm-ID: 320391 [Multi-domain]  Cd Length: 272  Bit Score: 130.18  E-value: 2.23e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILkAGAVFLKDAALFHSDDTDHCSfstvlCKVSVAASH 146
Cdd:cd15263   6 TIYFIGYSLSLVALSLALWIFLYFKDLRCLRNTIHTNLMFTYIL-ADLTWILTLTLQVSIGEDQKS-----CIILVVLLH 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 147 FATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCK------------LAFEDIAC-WDLDD 213
Cdd:cd15263  80 YFHLTNFFWMFVEGLYLYMLVVETFSGENIKLRVYAFIGWGIPAVVIVIWAIVKalaptapntaldPNGLLKHCpWMAEH 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 214 tsPYWWIIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQgSLHTQsQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLGIR 293
Cdd:cd15263 160 --IVDWIFQGPAILVLAVNLVFLVRIMWVLITKLRSAN-TVETQ-QYRKAAKALLVLIPLLGITYILVIAGPTEGIAANI 235
                       250       260       270
                ....*....|....*....|....*....|....*
gi 10242292 294 LP-LELGLGSFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15263 236 FEyVRAVLLSTQGFTVALFYCFLNTEVRNTLRHHF 270
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
74-327 1.06e-31

insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of hormone receptors; member of the class B secretin-like seven-transmembrane G protein-coupled receptors; This subgroup includes a neuropeptide receptor found in Bombyx mori (silk worm) and its closely related proteins from arthropods. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 320390 [Multi-domain]  Cd Length: 270  Bit Score: 120.24  E-value: 1.06e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  74 SISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDA-----ALFHSDDTDHCSFSTVLCKVSVAASHFA 148
Cdd:cd15262  13 SVSVVTSLPAVFIFYSYKRLRITRVILHRNLLISIIIRNILVIISKVfvildALTSSGDDTVMNQNAVVCRLLSIFERAA 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 149 TMTNFSWLLAEAVYLNCLLAST---SPSSRrafwWLVLAGWGLPVLFTGTWVSCKLAFEDIACWdLDDTSPYWWIIKGPI 225
Cdd:cd15262  93 RNAVFACMFVEGFYLHRLIVAVfaeKSSIR----FLYVIGAVLPLFPVIIWAIIRALHNDHSCW-VVDIEGVQWVLDTPR 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 226 VLSVGVNFGLFLNIIRILVRKLEpaqgSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLP---DNAGLGIRLPLELGLGS 302
Cdd:cd15262 168 LFILLVNTVLLVDIIRVLVTKLR----NTEENSQTKSTTRATLFLVPLFGLHFVITAYRPstdDCDWEDIYYYANYLIEG 243
                       250       260
                ....*....|....*....|....*
gi 10242292 303 FQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15262 244 LQGFLVAILFCYINKEVHYLIKNTY 268
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
67-320 3.71e-22

orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; group V adhesion GPCRs include orphan receptors GPR133, GPR144, and closely related proteins. The function of GPR144 has not yet been characterized, whereas GPR133 is highly expressed in the pituitary gland and is coupled to the G(s) protein, leading to activation of adenylate cyclase pathway. Moreover, genetic variations in the GPR133 have been reported to be associated with adult height and heart rate. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320599 [Multi-domain]  Cd Length: 252  Bit Score: 93.93  E-value: 3.71e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHsddtdhcsfsTVLCKVSVAASH 146
Cdd:cd15933   6 IISYIGCGISIACLALTLIIFLVLRVLSSDRFQIHKNLCVALLLAQILLLAGEWAEGN----------KVACKVVAILLH 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 147 FATMTNFSWLLAEAV--YLNCLLASTSPSSRRAFwwlVLAGWGLPVLFTGTWVSckLAFEDIA----CWdLDDTSPYWWI 220
Cdd:cd15933  76 FFFMAAFSWMLVEGLhlYLMIVKVFNYKSKMRYY---YFIGWGLPAIIVAISLA--ILFDDYGspnvCW-LSLDDGLIWA 149
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 221 IKGPIVLSVGVNFGLFLNIIRILVRK-LEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYiIFNFLPDNAGLGIRLPLELG 299
Cdd:cd15933 150 FVGPVIFIITVNTVILILVVKITVSLsTNDAKKSQGTLAQIKSTAKASVVLLPILGLTW-LFGVLVVNSQTIVFQYIFVI 228
                       250       260
                ....*....|....*....|.
gi 10242292 300 LGSFQGFIVAILYCFLNQEVR 320
Cdd:cd15933 229 LNSLQGLMIFLFHCVLNSEVR 249
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
67-320 1.07e-18

adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G protein-coupled receptors; The B2 subfamily of class B GPCRs consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320168 [Multi-domain]  Cd Length: 253  Bit Score: 84.16  E-value: 1.07e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHcprnyvhtQLFTTFILK--AGAVFLKDAALFHSDDTDHcsfSTVLCKVSVAA 144
Cdd:cd15040   6 IITYIGCGLSLLGLLLTIITYILFRKLR--------KRKPTKILLnlCLALLLANLLFLFGINSTD---NPVLCTAVAAL 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 145 SHFATMTNFSWLLAEAVYLNCLLAST-SPSSRRAFWWLVLAGWGLP---VLFTGTWVSCKLAFEDIACWdLDDTSPYWWI 220
Cdd:cd15040  75 LHYFLLASFMWMLVEALLLYLRLVKVfGTYPRHFILKYALIGWGLPliiVIITLAVDPDSYGNSSGYCW-LSNGNGLYYA 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 221 IKGPIVLSVGVNFGLFLNIIRILVRKlePAQGSLHTQSQYWRLSKSTLFLIPLFGIHYI--IFNFLPDNAGLGIrlpLEL 298
Cdd:cd15040 154 FLGPVLLIILVNLVIFVLVLRKLLRL--SAKRNKKKRKKTKAQLRAAVSLFFLLGLTWIfgILAIFGARVVFQY---LFA 228
                       250       260
                ....*....|....*....|..
gi 10242292 299 GLGSFQGFIVAILYCFLNQEVR 320
Cdd:cd15040 229 IFNSLQGFFIFIFHCLRNKEVR 250
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
63-328 1.18e-14

invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane G protein-coupled receptors; This subgroup includes latrophilin-like proteins that are found in invertebrates such as insects and worms. Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of vertebrate latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320556 [Multi-domain]  Cd Length: 259  Bit Score: 73.07  E-value: 1.18e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  63 STVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQL-FTTFIlkAGAVFLkdAALFHSDDTDHCSFSTVLCkvs 141
Cdd:cd15440   2 SALTFITYIGCIISIVCLLLAFITFTCFRNLQCDRNTIHKNLcLCLLI--AEIVFL--LGIDQTENRTLCGVIAGLL--- 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 142 vaasHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTG--TWVSCKLAFEDIACWdLDDTSPYWW 219
Cdd:cd15440  75 ----HYFFLAAFSWMLLEGFQLYVMLVEVFEPEKSRIKWYYLFGYGLPALIVAvsAGVDPTGYGTEDHCW-LSTENGFIW 149
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 220 IIKGPIVLSVGVNFgLFLNIIRILVRKLEPAQGSLHTQSQYWRLS---KSTLFLIPLFGIHYiIFNFLPDNAGLGIRLPL 296
Cdd:cd15440 150 SFVGPVIVVLLANL-VFLGMAIYVMCRHSSRSASKKDASKLKNIRgwlKGSIVLVVLLGLTW-TFGLLFINQESIVMAYI 227
                       250       260       270
                ....*....|....*....|....*....|..
gi 10242292 297 ELGLGSFQGFIVAILYCFLNQEVRTEIsRKWH 328
Cdd:cd15440 228 FTILNSLQGLFIFIFHCVLNEKVRKEL-RRWL 258
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
64-327 8.44e-13

cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. Celsr3 is expressed in both the developing and adult mouse brain. It has been functionally implicated in proper neuron migration and axon guidance in the CNS.


Pssm-ID: 320557 [Multi-domain]  Cd Length: 254  Bit Score: 67.28  E-value: 8.44e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  64 TVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILkAGAVFLkdaalFHSDDTDhcsfSTVLCKVSVA 143
Cdd:cd15441   3 LLKIVTYIGIGISLVLLVIAFLVLSCLRGLQSNSNSIHKNLVACLLL-AELLFL-----LGINQTE----NLFPCKLIAI 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 144 ASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAFEDIA--CWdLDDTSPYWWII 221
Cdd:cd15441  73 LLHYFYLSAFSWLLVESLHLYRMLTEPRDINHGHMRFYYLLGYGIPAIIVGLSVGLRPDGYGNPdfCW-LSVNETLIWSF 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 222 KGPIVLSVGVNFGLFLNIIRILVRKlepAQGSLHTQSQYWRLsKSTLFLIPLFGIHYIiFNFLPDNAGLGIRLPLELGLG 301
Cdd:cd15441 152 AGPIAFVIVITLIIFILALRASCTL---KRHVLEKASVRTDL-RSSFLLLPLLGATWV-FGLLAVNEDSELLHYLFAGLN 226
                       250       260
                ....*....|....*....|....*.
gi 10242292 302 SFQGFIVAILYCFLNQEVRTEISRKW 327
Cdd:cd15441 227 FLQGLFIFLFYCIFNKKVRRELKNAL 252
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
63-325 1.19e-12

orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR144 is an orphan receptor that belongs to the group V adhesion-GPCRs together with GPR133. The function of GPR144 has not yet been characterized, whereas GPR133 is highly expressed in the pituitary gland and is coupled to the Gs protein, leading to activation of adenylyl cyclase pathway. Moreover, genetic variations in the GPR133 have been reported to be associated with adult height and heart rate. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320383 [Multi-domain]  Cd Length: 263  Bit Score: 67.18  E-value: 1.19e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  63 STVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLftTFILKAGAVFLKDAALFHSddtdhcsfSTVLCKVSV 142
Cdd:cd15255   2 ATLRTLSFIGCGVSLCALIVTFILFLAVGVPKSERTTVHKNL--IFALAAAEFLLMFSEWAKG--------NQVACWAVT 71
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 143 AASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGtwVSCKLAFEDIA----CWdLDDTSPYW 218
Cdd:cd15255  72 ALLHLFFLAAFSWMLVEGLLLWSKVVAVNMSEDRRMKFYYVTGWGLPVVIVA--VTLATSFNKYVadqhCW-LNVQTDII 148
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 219 WIIKGPIVLSVGVNFGLFLNIIRILV-------RKLEPAQGS-LHTQSQYWRLSKSTLFLIPLFGIHYIifnflpdnAGL 290
Cdd:cd15255 149 WAFVGPVLFVLTVNTFVLFRVVMVTVssarrraKMLTPSSDLeKQIGIQIWATAKPVLVLLPVLGLTWL--------CGV 220
                       250       260       270       280
                ....*....|....*....|....*....|....*....|
gi 10242292 291 GIRLP-----LELGLGSFQGFIVAILYCFLNQEVRTEISR 325
Cdd:cd15255 221 LVHLSdvwayVFITLNSFQGLYIFLVYAIYNSEVRNAIQR 260
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
68-326 1.53e-12

orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR133 is an orphan receptor that belongs to the group V adhesion-GPCRs together with GPR144. The function of GPR144 has not yet been characterized, whereas GPR133 is highly expressed in the pituitary gland and is coupled to the Gs protein, leading to activation of adenylyl cyclase pathway. Moreover, genetic variations in the GPR133 have been reported to be associated with adult height and heart rate. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320384 [Multi-domain]  Cd Length: 260  Bit Score: 66.87  E-value: 1.53e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  68 IYTVGHSISIVALFVAITILVALRRLHCPRN---YVHTQLftTFILKAGAVFLKDAALFHSddtdhcsfSTVLCKVSVAA 144
Cdd:cd15256   7 ITYVGCSLSIFCLAITLVTFAVLSSVSTIRNqryHIHANL--SFAVLVAQILLLISFRFEP--------GTLPCKIMAIL 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 145 SHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCKLAF--EDIACWdLDDTSPYWWIIK 222
Cdd:cd15256  77 LHFFFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYGIGWGSPLLICIISLTSALDSygESDNCW-LSLENGAIWAFV 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 223 GPIVLSVGVNFGLFLNIIRILVRkLEPAQGSLHTQSQYWRLS-KSTLFLIPLFGIHYIiFNFLPDNAGLGIRLPLELGLG 301
Cdd:cd15256 156 APALFVIVVNIGILIAVTRVISR-ISADNYKVHGDANAFKLTaKAVAVLLPILGSSWV-FGVLAVNTHALVFQYMFAIFN 233
                       250       260
                ....*....|....*....|....*
gi 10242292 302 SFQGFIVAILYCFLNQEVRTEISRK 326
Cdd:cd15256 234 SLQGFFIFLFHCLLNSEVRAAFKHK 258
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
67-325 2.33e-12

Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320673 [Multi-domain]  Cd Length: 258  Bit Score: 66.10  E-value: 2.33e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILkAGAVFLKDAalfhsDDTDHcsfsTVLCKVSVAASH 146
Cdd:cd16007   6 VITWVGIVISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFL-AELLFLIGI-----DKTQY----QIACPIFAGLLH 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 147 FATMTNFSWLLAEAVYLNCLLAST--SPSSRRAFWWlvLAGWGLPVLFTGtwVSCKLAFE----DIACWDLDDTSPYWWI 220
Cdd:cd16007  76 FFFLAAFSWLCLEGVQLYLMLVEVfeSEYSRKKYYY--LCGYCFPALVVG--ISAAIDYRsygtEKACWLRVDNYFIWSF 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 221 IkGPIVLSVGVNFGLFLNIIRILVRK---LEPAQGSLHtQSQYWRLSKSTLFLipLFGIHYiIFNFLPDNAGLGIRLPLE 297
Cdd:cd16007 152 I-GPVSFVIVVNLVFLMVTLHKMIRSssvLKPDSSRLD-NIKSWALGAITLLF--LLGLTW-AFGLLFINKESVVMAYLF 226
                       250       260
                ....*....|....*....|....*...
gi 10242292 298 LGLGSFQGFIVAILYCFLNQEVRTEISR 325
Cdd:cd16007 227 TTFNAFQGMFIFIFHCALQKKVHKEYSK 254
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
65-325 1.86e-11

Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320552 [Multi-domain]  Cd Length: 258  Bit Score: 63.66  E-value: 1.86e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  65 VKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILkAGAVFLKDAalfhsDDTDHcsfsTVLCKVSVAA 144
Cdd:cd15436   4 LFVITWVGIVISLVCLLICIFTFCFFRGLQTDRNTIHKNLCINLFI-AELLFLIGI-----NRTQY----TIACPIFAGL 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 145 SHFATMTNFSWLLAEAVYLNCLLAST--SPSSRRAFWWlvLAGWGLPVLFTGtwVSCKLAFE----DIACWDLDDTSPYW 218
Cdd:cd15436  74 LHFFFLAAFCWLCLEGVQLYLLLVEVfeSEYSRRKYFY--LCGYSFPALVVA--VSAAIDYRsygtEKACWLRVDNYFIW 149
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 219 WIIkGPIVLSVGVNFGLFLNIIRILVR--KLEPAQGSLHTQSQYWRL-SKSTLFLIPL---FGIHYIifnflpdNAGLGI 292
Cdd:cd15436 150 SFI-GPVTFVITLNLVFLVITLHKMVShsDLLKPDSSRLDNIKSWALgAIALLFLLGLtwsFGLMFI-------NEESVV 221
                       250       260       270
                ....*....|....*....|....*....|...
gi 10242292 293 RLPLELGLGSFQGFIVAILYCFLNQEVRTEISR 325
Cdd:cd15436 222 MAYLFTIFNAFQGVFIFIFHCALQKKVRKEYSK 254
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
67-327 2.23e-11

epidermal growth factor-like module-containing mucin-like hormone receptors, member of the class B2 family of seven-transmembrane G protein-coupled receptors; group II adhesion GPCRs, including the epidermal growth factor (EGF)-module-containing, mucin-like hormone receptor (EMR1-4) and the leukocyte cell-surface antigen CD97, are primarily expressed in cells of the immune system. All EGF-TM7 receptors, which belong to the B2 subfamily of adhesion GPCRs, are members of group II, except for ETL (EGF-TM7-latrophilin related protein), which is classified into group I. Members of the EGF-TM7 receptors are characterized by the presence of varying number of N-terminal EGF-like domains, which play critical roles in ligand recognition and cell adhesion, linked by a stalk region to a class B seven-transmembrane domain. In the case of EMR2, alternative splicing results in four isoforms possessing either two (EGF1,2), three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. EMR2 shares strong sequence homology with CD97, differing by only six amino acids. CD97 is widely expressed on lymphocytes, monocytes, macrophages, dendritic cells, granulocytes and smooth muscle cells as well as in a variety of human tumors including colorectal, gastric, esophageal pancreatic, and thyroid carcinoma. However, unlike CD97, EMR2 is not found in those of CD97-positive tumor cells and is not expressed on lymphocytes but instead on monocytes, macrophages and granulocytes. CD97 has three known ligands: CD55, decay-accelerating factor for regulation of complement system; chondroitin sulfate, a glycosaminoglycan found in the extracellular matrix; and the integrin alpha5beta1, which play a role in angiogenesis. Although EMR2 does not effectively interact with CD55, the fourth EGF-like domain of this receptor binds to chondroitin sulfate to mediate cell attachment.


Pssm-ID: 320555 [Multi-domain]  Cd Length: 263  Bit Score: 63.51  E-value: 2.23e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLfttfilkAGAVFLKDAA-LFHSDDTDHcsfsTVLCKVSVAAS 145
Cdd:cd15439   6 VITYVGLIISLLCLFLAILTFLLCRSIRNTSTSLHLQL-------SLCLFLADLLfLVGIDRTDN----KVLCSIIAGFL 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 146 HFATMTNFSWLLAEAVYL-----NCLLASTSPSSRRAFWWLVLAGWGLPVLFTGtwVSCKLAFEDIA----CWdLDDTSP 216
Cdd:cd15439  75 HYLFLACFAWMFLEAVHLfltvrNLKVVNYFSSHRFKKRFMYPVGYGLPAVIVA--ISAAVNPQGYGtpkhCW-LSMEKG 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 217 YWWIIKGPIVLSVGVNFGLFLNIIRILVRKLepaqGSLHTQSQYWRLSKSTLF--LIPLF--GIHYI--IFNFLPDNAGL 290
Cdd:cd15439 152 FIWSFLGPVCVIIVINLVLFCLTLWILREKL----SSLNAEVSTLKNTRLLTFkaIAQLFilGCTWIlgLFQVGPVATVM 227
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 10242292 291 GIRLPLelgLGSFQGFIVAILYCFLNQEVRtEISRKW 327
Cdd:cd15439 228 AYLFTI---TNSLQGVFIFLVHCLLNRQVR-EEYRRW 260
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
64-325 1.28e-10

CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; group II adhesion GPCRs, including the leukocyte cell-surface antigen CD97 and the epidermal growth factor (EGF)-module-containing, mucin-like hormone receptor (EMR1-4), are primarily expressed in cells of the immune system. All EGF-TM7 receptors, which belong to the B2 subfamily B2 of adhesion GPCRs, are members of group II, except for ETL (EGF-TM7-latrophilin related protein), which is classified into group I. Members of the EGF-TM7 receptors are characterized by the presence of varying numbers of N-terminal EGF-like domains, which play critical roles in ligand recognition and cell adhesion, linked by a stalk region to a class B seven-transmembrane domain. In the case of CD97, alternative splicing results in three isoforms possessing either three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. For example, CD97, which is involved in angiogenesis and the migration and invasion of tumor cells, has been shown to promote cell aggregation in a GPS proteolysis-dependent manner. CD97 is widely expressed on lymphocytes, monocytes, macrophages, dendritic cells, granulocytes and smooth muscle cells as well as in a variety of human tumors including colorectal, gastric, esophageal pancreatic, and thyroid carcinoma. EMR2 shares strong sequence homology with CD97, differing by only six amino acids. However, unlike CD97, EMR2 is not found in those of CD97-positive tumor cells and is not expressed on lymphocytes but instead on monocytes, macrophages and granulocytes. CD97 has three known ligands: CD55, decay-accelerating factor for regulation of complement system; chondroitin sulfate, a glycosaminoglycan found in the extracellular matrix; and the integrin alpha5beta1, which play a role in angiogenesis. Although EMR2 does not effectively interact with CD55, the fourth EGF-like domain of this receptor binds to chondroitin sulfate to mediate cell attachment.


Pssm-ID: 320554 [Multi-domain]  Cd Length: 261  Bit Score: 61.32  E-value: 1.28e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  64 TVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILkAGAVFLKDAalfhsddtdHCSFSTVLCKVSVA 143
Cdd:cd15438   3 PLTLITKVGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLSLFL-AHLIFLLGI---------NNTNNQVACAVVAG 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 144 ASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTG--TWVSCKLAFEDIACWdLDDTSPYWWII 221
Cdd:cd15438  73 LLHYFFLAAFCWMSLEGVELYLMVVQVFNTQSLKKRYLLLIGYGVPLVIVAisAAVNSKGYGTQRHCW-LSLERGFLWSF 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 222 KGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPLFGIHYIIFNFLPDNAGLGIRLPLELgLG 301
Cdd:cd15438 152 LGPVCLIILVNAIIFVITVWKLAEKFSSINPDMEKLRKIRALTITAIAQLCILGCTWIFGFFQFSDSTLVMSYLFTI-LN 230
                       250       260
                ....*....|....*....|....
gi 10242292 302 SFQGFIVAILYCFLNQEVRTEISR 325
Cdd:cd15438 231 SLQGLFIFLLHCLLSKQVREEYSR 254
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
67-316 2.48e-10

seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.


Pssm-ID: 410628 [Multi-domain]  Cd Length: 267  Bit Score: 60.52  E-value: 2.48e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSDDTdhcSFSTVLCKVSVAASH 146
Cdd:cd14964   3 IILSLLTCLGLLGNLLVLLSLVRLRKRPRSTRLLLASLAACDLLASLVVLVLFFLLGLTEAS---SRPQALCYLIYLLWY 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 147 FATMTNFSWLLAEAVYLNCLLAS----TSPSSRRAFWWLVLAGWGLPVLFT--GTWVSCKLAFEDIACWDLDDTSP---- 216
Cdd:cd14964  80 GANLASIWTTLVLTYHRYFALCGplkyTRLSSPGKTRVIILGCWGVSLLLSipPLVGKGAIPRYNTLTGSCYLICTtiyl 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 217 YWWIIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTQSQY-WRLSKSTLFLIPLF-------GIHYIIFNFLPDNA 288
Cdd:cd14964 160 TWGFLLVSFLLPLVAFLVIFSRIVLRLRRRVRAIRSAASLNTDKnLKATKSLLILVITFllcwlpfSIVFILHALVAAGQ 239
                       250       260
                ....*....|....*....|....*...
gi 10242292 289 GLGIRLPLELGLGSFQGFIVAILYCFLN 316
Cdd:cd14964 240 GLNLLSILANLLAVLASTLNPFIYCLGN 267
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
64-320 2.17e-09

Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. Celsr3 is expressed in both the developing and adult mouse brain. It has been functionally implicated in proper neuronal migration and axon guidance in the CNS. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320659 [Multi-domain]  Cd Length: 254  Bit Score: 57.54  E-value: 2.17e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  64 TVKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLfttfilkAGAVFLKDAALFHSDDTDHCSFstvLCKVSVA 143
Cdd:cd15993   3 TLAIVTYSSVSASLAALVLTFSVLTCLRGLKSNTRGIHSNI-------AAALFLSELLFLLGINRTENQF---LCTVVAI 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 144 ASHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSckLAFEDIA----CWdLDDTSPYWW 219
Cdd:cd15993  73 LLHYFFLSTFAWLFVQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVG--LDPEGYGnpdfCW-ISIHDKLVW 149
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 220 IIKGPIVLSVGVNFGLFLNIIRILVrklEPAQGSLHTQSQYWRLSKStlFLIPLFGIHYIIFNFLPDNAGLGIRLPLELG 299
Cdd:cd15993 150 SFAGPIVVVIVMNGVMFLLVARMSC---SPGQKETKKTSVLMTLRSS--FLLLLLISATWLFGLLAVNNSVLAFHYLHAI 224
                       250       260
                ....*....|....*....|.
gi 10242292 300 LGSFQGFIVAILYCFLNQEVR 320
Cdd:cd15993 225 LCCLQGLAVLLLFCVLNEEVQ 245
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
65-325 1.40e-08

Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; Group I adhesion GPCRs consist of latrophilins (also called lectomedins or latrotoxin receptors) and ETL (EGF-TM7-latrophilin-related protein. These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320380 [Multi-domain]  Cd Length: 257  Bit Score: 55.20  E-value: 1.40e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  65 VKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILkAGAVFLkdaalFHSDDTDHcsfsTVLCKVSVAA 144
Cdd:cd15252   4 LTRITQVGIIISLVCLAICIFTFWFFRGLQSDRTTIHKNLCISLFL-AELVFL-----IGINTTTN----KIFCSVIAGL 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 145 SHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGtwVSCKLAFE----DIACWDLDDTSPYWWI 220
Cdd:cd15252  74 LHYFFLAAFAWMFIEGIQLYLMLVEVFENEGSRHKNFYIFGYGSPAVIVG--VSAALGYRyygtTKVCWLSTENYFIWSF 151
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 221 IkGPIVLSVGVNFgLFLNIIRILVRKLEPAQGSLHTQSQYWR-LSKSTLFLIPLFGIHYiIFNFLPDNAGLGIRLPLELG 299
Cdd:cd15252 152 I-GPATLIILLNL-IFLGVAIYKMFRHTAGLKPEVSCLENIRsWARGAIALLFLLGLTW-IFGVLHINHASVVMAYLFTV 228
                       250       260
                ....*....|....*....|....*.
gi 10242292 300 LGSFQGFIVAILYCFLNQEVRTEISR 325
Cdd:cd15252 229 SNSLQGMFIFLFHCVLSRKVRKEYYK 254
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
67-327 1.96e-07

EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; group II adhesion GPCRs, including the leukocyte cell-surface antigen CD97 and the epidermal growth factor (EGF)-module-containing, mucin-like hormone receptor (EMR1-4), are primarily expressed in cells of the immune system. All EGF-TM7 receptors, which belong to the B2 subfamily B2 of adhesion GPCRs, are members of group II, except for ETL (EGF-TM7-latrophilin related protein), which is classified into group I. Members of the EGF-TM7 receptors are characterized by the presence of varying numbers of N-terminal EGF-like domains, which play critical roles in ligand recognition and cell adhesion, linked by a stalk region to a class B seven-transmembrane domain. In the case of CD97, alternative splicing results in three isoforms possessing either three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. On the other hand, EMR2 generates four isoforms possessing either two (EGF1,2), three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. For example, CD97, which is involved in angiogenesis and the migration and invasion of tumor cells, has been shown to promote cell aggregation in a GPS proteolysis-dependent manner. CD97 is widely expressed on lymphocytes, monocytes, macrophages, dendritic cells, granulocytes and smooth muscle cells as well as in a variety of human tumors including colorectal, gastric, esophageal pancreatic, and thyroid carcinoma. EMR2 shares strong sequence homology with CD97, differing by only six amino acids. However, unlike CD97, EMR2 is not found in those of CD97-positive tumor cells and is not expressed on lymphocytes but instead on monocytes, macrophages and granulocytes. CD97 has three known ligands: CD55, decay-accelerating factor for regulation of complement system; chondroitin sulfate, a glycosaminoglycan found in the extracellular matrix; and the integrin alpha5beta1, which play a role in angiogenesis. Although EMR2 does not effectively interact with CD55, the fourth EGF-like domain of this receptor binds to chondroitin sulfate to mediate cell attachment.


Pssm-ID: 320597 [Multi-domain]  Cd Length: 262  Bit Score: 51.75  E-value: 1.96e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILkAGAVFLKDaalfhsddtDHCSFSTVLCKVSVAASH 146
Cdd:cd15931   6 WINRVGVIVSLFCLGLAIFTFLLCRWIPKINTTAHLHLCLCLSM-SHTLFLAG---------IEYVENELACTVMAGLLH 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 147 FATMTNFSWLLAEAVYLNCL---LASTSPSSRRAF--WWLVLAGWGLPVLFTG--TWVSCKLAFEDIACWdLDDTSPYWW 219
Cdd:cd15931  76 YLFLASFVWMLLEALQLHLLvrrLTKVQVIQRDGLprPLLCLIGYGVPFLIVGvsALVYSDGYGEAKMCW-LSQERGFNW 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 220 IIKGPIVLSVGVNFGLFLNIIRILVRKLEPAQGSLHTqsqywrLSKSTLFLIPLFGIHYI-----IFNFLPDNAGLGIRL 294
Cdd:cd15931 155 SFLGPVIAIIGINWILFCATLWCLRQTLSNMNSDISQ------LKDTRLLTFKAVAQLFIlgctwVLGLFQTNPVALVFQ 228
                       250       260       270
                ....*....|....*....|....*....|...
gi 10242292 295 PLELGLGSFQGFIVAILYCFLNQEVRTEIsRKW 327
Cdd:cd15931 229 YLFTILNSLQGAFLFLVHCLLNKEVREEY-IKW 260
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
67-325 3.62e-07

orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Group VIII adhesion GPCRs include orphan GPCRs such as GPR56, GPR64, GPR97, GPR112, GPR114, and GPR126. GPR56 is involved in the regulation of oligodendrocyte development and myelination in the central nervous system via coupling to G(12/13) proteins, which leads to the activation of RhoA GTPase. GPR126, on the other hand, is required for Schwann cells, but not oligodendrocyte myelination in the peripheral nervous system. Gpr64 is mainly expressed in the epididymis of male reproductive tract, and targeted deletion of GPR64 causes sperm stasis and efferent duct blockage due to abnormal fluid reabsorption, resulting in male infertility. GPR64 is also over-expressed in Ewing's sarcoma (ES), as well as upregulated in other carcinomas from kidney, prostate or lung, and promotes invasiveness and metastasis in ES via the upregulation of placental growth factor (PGF) and matrix metalloproteinase (MMP) 1. GPR97 is identified as a lymphatic adhesion receptor that is specifically expressed in lymphatic endothelium, but not in blood vascular endothelium, and is shown to regulate migration of lymphatic endothelial cells via the small GTPases RhoA and cdc42. GPR112 is specifically expressed in normal enterochromatin cells and gastrointestinal neuroendocrine carcinoma cells, but its biological function is unknown. GPR114 is mainly found in granulocytes (polymorphonuclear leukocytes), and GPR114-transfected cells induced an increase in cAMP levels via coupling to G(s) protein. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320386 [Multi-domain]  Cd Length: 267  Bit Score: 50.88  E-value: 3.62e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLhcPRNY---VHTQLFTTFILKAGAVFLKDA-ALFHSDDtdhcsfstvLCKVSV 142
Cdd:cd15258   6 FISYVGCGISAIFLAITILTYIAFRKL--RRDYpskIHMNLCAALLLLNLAFLLSSWiASFGSDG---------LCIAVA 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 143 AASHFATMTNFSWLLAEAVYLNCLLAST-SPSSRRAFWWLVLAGWGLP---VLFTGTWVSCKLAFEDIACWDLDDTSPYW 218
Cdd:cd15258  75 VALHYFLLACLTWMGLEAFHLYLLLVKVfNTYIRRYILKLCLVGWGLPallVTLVLSVRSDNYGPITIPNGEGFQNDSFC 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 219 WiIKGPIVLSVGV----------NFGLFLNIIRILVRKLEPAQGSLHTQSqyWRLSKSTLFLIPLFGIHY--IIFNFLPD 286
Cdd:cd15258 155 W-IRDPVVFYITVvgyfgltflfNMVMLATVLVQICRLREKAQATPRKRA--LHDLLTLLGLTFLLGLTWglAFFAWGPF 231
                       250       260       270
                ....*....|....*....|....*....|....*....
gi 10242292 287 NAglgIRLPLELGLGSFQGFIVAILYCFLNQEVRTEISR 325
Cdd:cd15258 232 NL---PFLYLFAIFNSLQGFFIFIWYCSMKENVRKQWRA 267
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
63-246 1.00e-06

Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G protein-coupled receptors; The subfamily B3 of class B GPCRs consists of Methuselah (Mth) and its closely related proteins found in bilateria. Mth was originally identified in Drosophila as a GPCR affecting stress resistance and aging. In addition to the seven transmembrane helices, Mth contains an N-terminal extracellular domain involved in ligand binding, and a third intracellular loop (IC3) required for the specificity of G-protein coupling. Drosophila Mth mutants showed an increase in average lifespan by 35% and greater resistance to a variety of stress factors, including starvation, high temperature, and paraquat-induced oxidative toxicity. Moreover, mutations in two endogenous peptide ligands of Methuselah, Stunted A and B, showed an increased in lifespan and resistance to oxidative stress induced by dietary paraquat. These results strongly suggest that the Stunted-Methuselah system plays important roles in stress response and aging.


Pssm-ID: 410632 [Multi-domain]  Cd Length: 270  Bit Score: 49.53  E-value: 1.00e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  63 STVKIIYTVGHSISIVALFVAITILVALRRLH-----CPRNYVHTqLFTTFILKAGAVFLKDAalfhsddtdhcsfSTVL 137
Cdd:cd15039   2 SILGILTLIGLIISLVFLLLTLAVYALLPELRnlhgkCLMCLVLS-LFVAYLLLLIGQLLSSG-------------DSTL 67
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 138 CKVSVAASHFATMTNFSWLLAEAVYLNCLLASTSP-----SSRRAFWWLVLAGWGLPVLFTGT-----WVSC----KLAF 203
Cdd:cd15039  68 CVALGILLHFFFLAAFFWLNVMSFDIWRTFRGKRSsssrsKERKRFLRYSLYAWGVPLLLVAVtiivdFSPNtdslRPGY 147
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 10242292 204 EDIACWDLDDTSPYWWIIkGPIVLSVGVNFGLF-LNIIRILVRK 246
Cdd:cd15039 148 GEGSCWISNPWALLLYFY-GPVALLLLFNIILFiLTAIRIRKVK 190
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
67-325 2.34e-06

Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320671 [Multi-domain]  Cd Length: 258  Bit Score: 48.40  E-value: 2.34e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILkAGAVFLkdAALFHSDdtdhcsfSTVLCKVSVAASH 146
Cdd:cd16005   6 VITWVGILLSLVCLLICIFTFCFFRGLQSDRNTIHKNLCISLFV-AELLFL--IGINRTD-------QPIACAVFAALLH 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 147 FATMTNFSWLLAEAVYLNCLLAST--SPSSRRAFWWLVlaGWGLPVLFTG--TWVSCKLAFEDIACWDLDDTSPYWWIIk 222
Cdd:cd16005  76 FFFLAAFTWMFLEGVQLYIMLVEVfeSEHSRRKYFYLV--GYGMPALIVAvsAAVDYRSYGTDKVCWLRLDTYFIWSFI- 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 223 GPIVLSVGVN---FGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSKSTLFLIPL---FGIHYIifnflpdNAGLGIRLPL 296
Cdd:cd16005 153 GPATLIIMLNvifLGIALYKMFHHTAILKPESGCLDNIKSWVIGAIALLCLLGLtwaFGLMYI-------NESTVIMAYL 225
                       250       260
                ....*....|....*....|....*....
gi 10242292 297 ELGLGSFQGFIVAILYCFLNQEVRTEISR 325
Cdd:cd16005 226 FTIFNSLQGMFIFIFHCVLQKKVRKEYGK 254
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
65-320 4.58e-06

Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320657 [Multi-domain]  Cd Length: 254  Bit Score: 47.53  E-value: 4.58e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  65 VKIIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTtfilkagAVFLKDAALFHSDDTDHCSFstvLCKVSVAA 144
Cdd:cd15991   4 LKIITYTTVSLSLVALLITFILLVLIRTLRSNLHSIHKNLVA-------ALFFSELIFLIGINQTENPF---VCTVVAIL 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 145 SHFATMTNFSWLLAEAVYLNCLLASTSPSSRRAFWWLVLAGWGLPVLFTGTWVSCK---LAFEDIaCW-DLDDTspYWWI 220
Cdd:cd15991  74 LHYFYMSTFAWMFVEGLHIYRMLTEVRNINTGHMRFYYVVGWGIPAIITGLAVGLDpqgYGNPDF-CWlSVQDT--LIWS 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 221 IKGPIVLSVGVNFGLFLNIIRILVRKLEpaqgslHTQSQYWRLSK-STLFLIPLFGIHYIIFNFLPDNAGLGIRLPLELG 299
Cdd:cd15991 151 FAGPIGIVVIINTVIFVLAAKASCGRRQ------RYFEKSGVISMlRTAFLLLLLISATWLLGLMAVNSDTLSFHYLFAI 224
                       250       260
                ....*....|....*....|.
gi 10242292 300 LGSFQGFIVAILYCFLNQEVR 320
Cdd:cd15991 225 FSCLQGIFIFFFHCIFNKEVR 245
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
67-325 6.51e-06

Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320672 [Multi-domain]  Cd Length: 258  Bit Score: 46.83  E-value: 6.51e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  67 IIYTVGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILkAGAVFLkdaalFHSDDTDHcsfsTVLCKVSVAASH 146
Cdd:cd16006   6 VITWVGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFI-AEFIFL-----IGIDKTEY----KIACPIFAGLLH 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 147 FATMTNFSWLLAEAVYLNCLLAST--SPSSRRAFWWlvLAGWGLPVLFTGtwVSCKLAFEDI----ACWdLDDTSPYWWI 220
Cdd:cd16006  76 FFFLAAFAWMCLEGVQLYLMLVEVfeSEYSRKKYYY--VAGYLFPATVVG--VSAAIDYKSYgtekACW-LRVDNYFIWS 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 221 IKGPivlsvgVNFGLFLNIIRILVRKLEPAQGSLHTQSQYWRLSK------STLFLIPLFGIHYiIFNFLPDNAGLGIRL 294
Cdd:cd16006 151 FIGP------VTFIILLNLIFLVITLCKMVKHSNTLKPDSSRLENikswvlGAFALLCLLGLTW-SFGLLFINEETIVMA 223
                       250       260       270
                ....*....|....*....|....*....|.
gi 10242292 295 PLELGLGSFQGFIVAILYCFLNQEVRTEISR 325
Cdd:cd16006 224 YLFTIFNAFQGMFIFIFHCALQKKVRKEYSK 254
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
68-191 7.36e-05

orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR114 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include GPR56, GPR64, GPR97, GPR112, and GPR126. GPR114 is mainly found in granulocytes (polymorphonuclear leukocytes), and GPR114-transfected cells induced an increase in cAMP levels via coupling to G(s) protein. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320559 [Multi-domain]  Cd Length: 268  Bit Score: 43.98  E-value: 7.36e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  68 IYTVGHSISIVALFvaITILVALRRLHCPRN---YVHTQLFTTFILKAGAVFLKDAALFhsddtdhcSFSTVLCKVSVAA 144
Cdd:cd15443   7 ISIVGCSISAAASL--LTILLHFFSRKQPKDsttRIHMNLLGSLFLLNGSFLLSPPLAT--------SQSTWLCRAAAAL 76
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 10242292 145 SHFATMTNFSWLLAEAVYLNCLLASTSPSS-RRAFWWLVLAGWGLPVL 191
Cdd:cd15443  77 LHYSLLCCLTWMAIEGFHLYLLLVKVYNIYiRRYVLKLCVLGWGLPAL 124
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
71-320 5.71e-03

brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Brain-specific angiogenesis inhibitors (BAI1-3) constitute the group VII of cell-adhesion receptors that have been implicated in vascularization of glioblastomas. They belong to the B2 subfamily of class B GPCRs, are predominantly expressed in the brain, and are only present in vertebrates. Three BAIs, like all adhesion receptors, are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. For example, BAI1 N-terminus contain an integrin-binding RGD (Arg-Gly-Asp) motif in addition to five thrombospondin type 1 repeats (TSRs), which are known to regulate the anti-angiogenic activity of thrombospondin-1, whereas BAI2 and BAI3 have four TSRs, but do not possess RGD motifs. The TSRs are functionally involved in cell attachment, activation of latent TGF-beta, inhibition of angiogenesis and endothelial cell migration. The TSRs of BAI1 mediate direct binding to phosphatidylserine, which enables both recognition and internalization of apoptotic cells by phagocytes. Thus, BAI1 functions as a phosphatidylserine receptor that forms a trimeric complex with ELMO and Dock180, leading to activation of Rac-GTPase which promotes the binding and phagocytosis of apoptotic cells. BAI3 can also interact with the ELMO-Dock180 complex to activate the Rac pathway and can also bind to secreted C1ql proteins of the C1Q complement family via its N-terminal TSRs. BAI3 and its ligands C1QL1 are highly expressed during synaptogenesis and are involved in synapse specificity. Moreover, BAI2 acts as a transcription repressor to regulate vascular endothelial growth factor (VEGF) expression through interaction with GA-binding protein gamma (GABP). The N-terminal extracellular domains of all three BAIs also contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain, which undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif to generate N- and C-terminal fragments (NTF and CTF), a putative hormone-binding domain (HBD), and multiple N-glycosylation sites. The C-terminus of each BAI subtype ends with a conserved Gln-Thr-Glu-Val (QTEV) motif known to interact with PDZ domain-containing proteins, but only BAI1 possesses a proline-rich region, which may be involved in protein-protein interactions.


Pssm-ID: 320379  Cd Length: 253  Bit Score: 38.00  E-value: 5.71e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292  71 VGHSISIVALFVAITILVALRRLHCPRNYVHTQLFTTFILKAGAVFLKDAALFHSddtdhcsfsTVLCKVSVAASHFATM 150
Cdd:cd15251  10 VGCGVSCLALLTLLAIYAAFWRYIRSERSIILINFCLSIISSNILILVGQTQTLN---------KGVCTMTAAFLHFFFL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 151 TNFSWLLAEA--VYLNCLLASTSPSSRRAFWWLvlaGWGLPVLFTGTWVS---CKLAFEDIACWdLDDTSPYWWIIKGPI 225
Cdd:cd15251  81 SSFCWVLTEAwqSYMAVTGRMRTRLIRKRFLCL---GWGLPALVVAVSVGftrTKGYGTSSYCW-LSLEGGLLYAFVGPA 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 10242292 226 VLSVGVNFglflnIIRILV-RKLEPAQGSL-HTQSQYWrlskSTLFLIPLFGIHYIIFNFLPDNAGLGIRLPLELGLGSF 303
Cdd:cd15251 157 AAVVLVNM-----VIGILVfNKLVSRDGISdNAMASLW----SSCVVLPLLALTWMSAVLAMTDRRSVLFQILFAVFDSL 227
                       250
                ....*....|....*..
gi 10242292 304 QGFIVAILYCFLNQEVR 320
Cdd:cd15251 228 QGFVIVMVHCILRREVQ 244
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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